E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients ( ≥18 and ≤ 70 years) ≥ 1 year after single, double or heart/lung transplantation. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to - Improvement of adherence as measured by Tacrolimus trough level below the target level and dispensing of less than 50% of the prescribed doses in the last three days measured electronically before this subtherapeutic drug monitoring |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• Deterioration of graft function as defined as more than 20% decline in maximum FEV1 before and at month 12 after conversion • Number of drug holidays (intake of less than 50% of prescribed doses in 24 hours) measured electronically • Evaluation of renal function in pts converted from CyA to Tac in combination with MMF and steroids as assessed by serum creatinine, creatinine clearance (Cockgroft Gault), MDRD and Cystatin C before and at month 1, 3, 6 and 12 after conversion • Evaluation of cardiovascular risk factors (hypertension, hyperlipidaemia, hypertriglyceridemia, diabetes mellitus) • Incidence of CMV infections and other infections • Efficacy: Incidence of acute rejection episodes, graft and patient survival • Safety: Incidence of adverse events • Comparison of MPA-mini-AUC under Tacrolimus once and twice daily administration
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Pts more than1 year after single lung, double lung or heart/lung transplantation and • Pts treated with ciclosporin, steroids and MMF and • Pts ≥18 and ≤ 70 years and • Pts with one oft he following • Pts with recurrent acute rejections (RAR) two or more acute rejections in 3 months (first 3 years post Tx, 6 months (>3 years post Tx) defined by • transbronchial biopsy >A1 (or A1 with clinical criteria below)nach ISHLT (B>1R) or • decline of FEV1 > 10 % baseline after exclusion of infection, airway complication, effusion etc. and improvement to steroid-pulse therapy (methylprednisolone 15 mg/kg for three days) = FEV1 improvement > 10% compared to the last measurement before AR treatment • Pts with steroid-resistant or ongoing acute rejections (OAR) defined by transbronchial biopsy >A1 (or A1 with clinical criteria above) at least 4 weeks following steroid-pulse therapy (methylprednisolone 15 mg/kg for three days) or no FEV1 improvement (< 5% baseline) at least 14 days following ACR steroid-pulse therapy (methylprednisolone 15 mg/kg for three days) after exclusion of infection, airway complication, effusion etc. or • Pts with new onset of BOS (nBOS) Unexplained FEV1 < 80% of baseline after exclusion of Infection, airway complication, effusion etc • Pts with CyA associated side effects (e.g. hyperlipidaemia, hypertriglyceridemia, hypertension, hirsutism, gingival hyperplasia)
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E.4 | Principal exclusion criteria |
• Pregnant or breast feeding women • Pts who are not using a double-barrier method of birth control • Pts with systemic infections • Pts with severe diarrhea, vomiting, active ulcer • Pts with severe liver disease or liver cirrhosis • Pts with m-Tor inhibitors • Pts with hypersensitivity to Tacrolimus, other macrolides or other tablet ingredients.
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients of the once daily administration group of the immunsupressive medication will have a better compliance compared to the twice daily group (as measured by the endpoints variability and medication abstraction from the electronic devices) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
Prograf (Tacrolimus administred twice daily) |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |